Synthesis and Determination of Absolute Configuration of α-Pyrones Isolated from Penicillium corylophilum

The first total synthesis of (S)-6-(2,9-dihydroxynonyl)-4-hydroxy-3-methyl-2H-pyran-2-one, 4-hydroxy-3-methyl-6-((2S,4R)-2,4,11-trihydroxyundecyl)-2H-pyran-2-one, and its unnatural 2R,4R-isomer starting from commercially available 1,8-octanediol is described. The synthesis led to the revision of the proposed structural assignment of the natural product as (R)-6-(2,9-dihydroxynonyl)-4-hydroxy-3-methyl-2H-pyran-2-one. The key steps include chiral auxiliary mediated asymmetric acetate aldol reaction, dianion addition, and base mediated cyclization to form an α-pyrone ring.